A Randomized, Multicenter, Open-Label, Phase 2b Study of VELCADE Alone and VELCADE Plus Irinotecan in Patients With Relapsed or Refractory Colorectal Carcinoma

Inclusion Criteria

Inclusion Criteria

- Patient has histologically confirmed inoperable locally advanced or metastatic CRC.

- Patient has measurable disease.

- Patient is not considered a candidate for immediate curative resection.

- Patient has received no more than 2 prior treatment regimens for metastatic disease,
one of which must have contained irinotecan.

- Patient has relapsed or progressed while receiving an irinotecan-containing regimen.

- Patient has KPS of 70% or greater.

- Patient has a life expectancy greater than 3 months.

- Patient is 18 years of age or older.

- Female patient is postmenopausal, surgically sterilized, or willing to use an
acceptable method of birth control (ie, a hormonal contraceptive, intrauterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.

- Male patient agrees to use an acceptable method of birth control for the duration of
the study.

- Patient has given voluntary written informed consent before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to his or her
future medical care.

- Patient is, in the investigator's opinion, willing and able to comply with the
protocol requirements.

Exclusion Criteria

- Patient has greater than or equal to Grade 2 neuropathy as defined by the NCI Common
Toxicity Criteria (CTC):

- Grade 2: Objective sensory loss or paresthesia (including tingling),
interfering with function, but not interfering with activities of daily living
(ADL).

- Grade 3: Sensory loss or paresthesia interfering with ADL.

- Grade 4: Permanent sensory loss that interferes with function.

- Patient has previously received treatment with VELCADE.

- Patient has other malignancies except non-melanoma skin cancers and carcinoma of the
cervix in situ.

- Patient has received chemotherapy within 4 weeks prior to enrollment.

- Patient has received radiation therapy within 4 weeks prior to enrollment.

- Patient has received monoclonal antibodies within 6 weeks prior to enrollment.

- Patient had major surgery within 4 weeks prior to enrollment.

- Patient has inadequate organ function at Baseline (ie, Day 1 of Cycle 1) as defined
by the following laboratory values:

- Platelet count ≤ 100,000 x 109/L

- Hemoglobin ≤ 8.0 g/dL

- Absolute neutrophil count (ANC) ≤ 1.5 x 109/L

- Aspartate transaminase (AST) ≥ 3 times the upper limit of the normal range (ULN)

- Alanine transaminase (ALT) ≥ 3 times ULN

- Total bilirubin ≥ 1.5 times ULN, unless clearly related to the disease

- Calculated or measured creatinine clearance ≤ 60 mL/minute.

- Patient has had a myocardial infarction within 6 months of enrollment or has New York
Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia or active conduction system abnormalities. Prior to study entry, any
electrocardiogram (ECG) abnormality at Screening has to be documented by the
investigator as not medically relevant.

- Patient has symptomatic brain metastases.

- Patient has an active systemic infection requiring treatment.

- Patient has a history of inflammatory bowel disease.

- Patient has a history of allergic reaction attributable to compounds containing boron
or mannitol.

- Patient previously required premature discontinuation of irinotecan therapy because
of drug-related toxicity.

- Patient is known to be human immunodeficiency virus (HIV)-positive. Patients
assessed by the investigator to be at risk for HIV infection should be tested in
accordance with local regulations.

- Patient is known to be hepatitis B surface antigen-positive or has known active
hepatitis C infection. Patients assessed by the investigator to be at risk for
hepatitis B or C infection should be tested in accordance with local regulations.

- Patient has poorly controlled hypertension, diabetes mellitus, or another serious
medical or psychiatric illness that could, in the investigator's opinion, potentially
interfere with the completion of treatment according to this protocol.

- Female patient is pregnant or breast-feeding. Confirmation that the patient is not
pregnant must be established by a negative serum β-human chorionic gonadotropin
(β-hCG) pregnancy test result obtained during the Screening period. Pregnancy
testing is not required for postmenopausal or surgically sterilized women.

- Patient currently is enrolled in another clinical research study or has received an
investigational agent for any reason within 4 weeks of enrollment.